1. Population Modeling by Examples Population Modeling Working Group popmodwkgrpimag-news@simtk.org SpringSim 2015 April 12 - 15, 2015 Alexandria, VA, USA

2. Population Modeling Working Group Background The Inter Agency Modeling and Analysis Group (IMAG) hosts a population modeling working group There was increased interest in the topic in 2014 MSM/IMAG meeting at the NIH We defined Population modeling as: “Modeling a collection of entities with different levels of heterogeneity“ We created a mailing list and asked people to join and share their research Here are some examples:

3. Population Modeling Working Group Systems Epidemiology – Tufts Percents of infants in a simulated population (N=1,000) born at the GA indicated who had bacteria (PLACBUG) and inflammation in the placenta (PLACINF). Simulated data (blue) compared to published values (red) from ~1080 placentas from the ELGAN study. Gestational Age (week) 2324252627 % Placbug % Placinf ? Simulation Published Durgham, Fried, Hescott & Dammann, in preparation

4. Population Modeling Working Group Simulate human population, add your own national or regional data Link lifestyle to diseases and health outcomes E.g. effect of overweight policy, what if UK weights in NL? Contact: Hendriek.Boshuizen@rivm.nl Talitha.Feenstra@rivm.nl www.dynamo-hia.eu Hendriek.Boshuizen@rivm.nl Talitha.Feenstra@rivm.nl www.dynamo-hia.eu Modeling in Support of Public Health Policy - RIVM

5. Population Modeling Working Group Explaining Mechanisms of Drug Induced Liver Injury C. Anthony Hunt, BioE, UCSF Represent & explain intra- & inter-individual mechanistic variability in DILI Methods are agent-oriented Components & spaces are concrete, biomimetic & nested Mechanistic events are networked within & across scales

6. Population Modeling Working Group Social Networks of Wild Mammals Amiyaal Ilany (Biology, University of Pennsylvania) Studying spotted hyenas and rock hyraxes Exploring network dynamics using Stochastic Agent- Based Models Finding that the social structure constraints its future dynamics and affects survival and mating patterns

7. Population Modeling Working Group Modeling Community Vulnerability and Medically Fragile Populations for Natural Disaster Preparedness Joshua G Behr & Rafael Diaz VA Modeling, Analysis, & Simulation Center Measure & map 17 dimensions of household vulnerability. Simulate storm scenarios, such as Super Storm Sandy, crossing the region, and measure damage and displaced persons. The merging of these two data streams informs our system dynamics models. Models produce short, medium, and long term forecasts of housing needs and demand for services, especially among medically fragile populations. Models allow for testing planning and policy interventions and measuring ROI under different preparedness scenarios.

8. Population Modeling Working Group Explores the dynamics of cholera outbreaks in Dadaab refugee camps The model integrates geographical data with agents' daily activities within a refugee ca mp. Agent Based Modeling of the Spread of Cholera Atesmachew Hailegiorgis and Andrew Crooks, George Mason University Results show cholera infections are impacted by agents' movement and source of contamination. Click here to see the YouTube Video

9. Population Modeling Working Group left tumor side right tumor side first transformed cell cancer gland fragments (2,000 to 10,000 cells) University of Southern California Zhao J, Siegmund KD, Shibata D, Marjoram P. "Ancestral inference in tumors: How much can we know?." Journal of theoretical biology 359 (2014): 136- 145. Same concept as phylogenetic inference Sample population of tumor cells from both tumor sides Build model for tumor growth Use patterns of relatedness between populations of cells to infer deep history of tumor ancestry (e.g. what happens just after a tumor has formed and is growing rapidly; how many stem cells does the tumor have). Ancestral inference in tumors

10. Population Modeling Working Group The SILAS model Sexual Infections as Large-scale Agent-based Simulation Stefan Scholz, University of Bielefeld, Germany Agent-based model in FLAME Simulates sexual behavior of humans for the analysis of STI-spreads Age-, sex-, sexual orientation- and relationship-status-specific, social, sexual and contraceptual behavior Behavior estimated via GLMs from panel datasets Pregnancy as internal result of sexual contacts to simulate perinatal infections

11. Papers at AAMAS ‘13, WSC ‘13, BDSE ‘13, SBP ‘13, and more No communication restoration, Pr(Sheltering|EBR) = 0.1 Partial comm restoration, Pr(Sheltering|EBR) = 0.1 No communication restoration, Pr(Sheltering|EBR) = 0.9 Partial comm restoration, Pr(Sheltering|EBR) = 0.9 EBR: Emergency Broadcast Received 1 3 2 4 A Large-Scale Simulation of a Behaving Human Population in the Aftermath of a Hypothetical Nuclear Detonation Christopher L. Barrett, Madhav V. Marathe, Stephen G. Eubank, Samarth Swarup, et al. Network Dynamics and Simulation Science Lab, Virginia Bioinformatics Institute, Virginia Tech Scenario: A 10kT IND is detonated at ground level Location: 16 th and K Street, Washington D.C., USA Day and Time: Tuesday, 11:15 a.m. The figure above shows the building damage and the expected path of the fallout cloud. Models interactions between individuals and infrastructures in the aftermath of a large human-initiated crisis. Model includes the population (with demographics and family structure), physical locations, and multiple infrastructures (transportation, cell phone communication, health, and power). Multiple human behaviors are modeled, including household reconstitution, shelter-seeking, healthcare-seeking, evacuation, panic, and aid&assist. The figure on the left shows a four-cell experiment investigating the effects of early (partial) restoration of communication on health outcomes. We suppose that emergency broadcasts are sent over the cell phone network, advising people to shelter in place. The probability that people will actually do so upon receiving the broadcasts is one of the parameters in the experiment. If communication if not restored, it doesn’t matter how likely people are to shelter upon receiving broadcasts, because the right people don’t get the broadcasts. Restoring communication helps even if people have a low probability of following advice to shelter. This is due to secondary benefits like helping people determine their families are safe. Communication restoration (an engineering intervention) combined with a high probability of sheltering (attainable through advance education/training of people) leads to a large health benefit.

12. Population Modeling Working Group Applications: Mental Health System Planning Mental Health System Resource Allocation Mental Health System Performance Measurement Computer Implemented, Markov Mental Health Simulation Model Steve Leff, Harvard Medical & Human Services Research Institute Service Utilization, Expenditures, Revenues

13. Population Modeling Working Group The Reference Model for Disease Progression Jacob Barhak Built from literature references and hence the name: The Reference Model Compares equations to populations from multiple studies /clinical trials A League / Consumers Report for disease models Current version deals with diabetic populations MI No CHDSurvive MI CHD Death Stroke No Stroke Survive Stroke Stroke Death Alive Other Death Death Process CHD Process Stroke Process Competing Mortality AB CD EF GH Pop 3Pop 2Pop 1 Eq EHEEEE… Eq ADABCD… Pop 1 4621 … Pop 2 2461 … Pop 3 2392 … ……………… Fitness Matrix

14. Population Modeling Working Group INSPYRED Evolutionary Computation Aaron Garrett - Jacksonville State University Generator Evaluator 3.17.54.25.2 Selector CrossoverMutation Variators Candidates Parents +=→ Repeat Terminator Best Solution Generations / Epocs

15. Population Modeling Working Group Discrete Event Simulation (DES) to value service improvement Service use  Costs & Glaucoma stability  QALYs & Service use  … Compare value of new technologies and service improvement Referred to service Wait for 1 st clinic visit Wait for intended time to next clinic Queue for clinic visit Wait for intended time to next clinic Queue for clinic visit Patients with booked clinic date Patients going onto waiting list Clinic visit Discharge or dead Prof Jon Karnon, University of Adelaide

16. Population Modeling Working Group Population modeling of environmentally transmitted and drug resistant pathogens Cristina Lanzas North Carolina State University Study infectious diseases dynamics of enteric pathogens (e.g. Clostridium difficile in humans, Shiga-toxin Escherichia coli in cattle) Methods: Compartmental, agent- based and network models. Models include detailed exposure patterns, individual and spatial heterogeneity relevant to disease transmission. http://www.cvm.ncsu.edu/dphp/personnel/lanzas.html

17. Population Modeling Working Group Recently created an open source Probabilistic Plug In for OpenSim to simulate uncertainty and population variability Difficult to simulate treatment effects that inform evidence based medicine in orthopaedics Monte Carlo simulations and efficient estimation methods to analyze the effects of experimental error and parameter uncertainty within patient-specific simulations Assessment of Rehabilitation-Based Effects by Simulating Treatment Effects and Randomized Controlled Trials with Population of Musculoskeletal Bradley Davidson, Casey Myers Kevin Shelburne, Peter Laz

18. Population Modeling Working Group Discussion on the Mailing List What constitutes population modeling? – Is “cohort modeling” in “population modeling”? Active members tend to distance from traditional cohort modeling and prefer newer technologies Yet there is still a spectrum of opinions within the group – Will modeling non human/animal entities such as cells or cell phones constitutes population modeling? This idea is in the current definition of the group

19. Population Modeling Working Group Join the Mailing List or Read the Mailing List Archives This presentation is indented for reuse by educators Please feel free to use this material while acknowledging the authors of slides you use. Mailing list is powered by simtk.orgsimtk.org Thanks to Joy Ku and the SimTk team https://simtk.org/mailman/listinfo/popmodwkgrpimag-news